Draft Drugs, Cosmetics and Medical Devices bill 2022 - A missed opportunity

 

                                    -        Ganadhish Kamat

 

Current Drugs & Cosmetics Act 1940 & Rules 1945 there under were enacted prior to independence when the drug development and manufacturing in India was in its infancy. Import was the main source of modern medicines and export was non-existent. Knowledge about Pharmaceutical science was also limited in pre independence days. The act and the rules are largely focused on administrative controls through licensing and surveillance through inspections, sampling, and testing. Many of the regulations have become outdated in light of new developments in the pharmaceutical science and some create hindrance in innovation and drug development. This the time for complete overhaul of the D&C Act and the Rules to make it more efficient and effective in ensuring quality and safety of the drugs in India and removing unnecessary burden on manufacturers and the enforcement agency.

During past one decade, India has become a major global supplier for both Active Ingredients (APIs) as well as finished dosage forms supplying high quality drugs to countries all over the globe and is being called as the Pharmacy of the world. This has become possible due to pharmaceutical companies adapting to the requirements & expectation of international regulatory guidelines with respect to the Quality standards of the drugs, standards of manufacturing facilities and Quality systems. However, quality of drugs being sold in India has not come up to the global standards because Indian drug laws have not been updated in line with global requirements. So, while India supplies high quality drugs to the world, Indian people are largely deprived of the same unless they use medicines from some responsible manufacturers who have adopted global standards for drugs distributed in India although not mandated by law.

Major flaws in current system are – The Drug approval process and Organization structure.

Drug approval process –

While Schedule Y of D&C rules, lays down procedure for clinical trials, bioequivalence studies and new drug approval, this is applicable only for new drugs and subsequent applications for same drug till 4 years from first approval of the new drug by DCGI. After this period, state licensing authorities can grant manufacturing license to any company for manufacturing that drug which has facility meeting GMP requirements based on submission of certain documents which are largely administrative in nature and which differ widely from state to state. No scientific evaluation of development and other technical data is done to ensure that the product will remain effective and safe throughout its shelf life. This 4-year period has no scientific rationale as each formulation can be different and hence need to be evaluated individually to assess its safety and efficacy. After 4 years, companies don’t have to submit Bio Equivalence (BE) data in lieu of clinical data to prove efficacy of drugs. Although DCGI has issued circular to state agencies making BE study mandatory for certain classes of drugs, this is not being followed in most states as State Drug Control Organizations are not directly reporting to Central Drug control office. Many state agencies do not require important information necessary to ensure safety of the drug such as impurity profiles, stability data to be submitted as part of application. They also don’t insist that the product specifications include important tests like dissolution, related substances and residual solvents etc. which are critical for ensuring safety and efficacy of the drugs, unless they are part of Pharmacopeial monographs. Because of this lack of controls, there is no guarantee that the drugs distributed in India are safe and effective.

Current system of controlling manufacturing through licensing process rather than controlling distribution through Marketing Authorization (MA) as done in most of the countries, delays availability of drugs and creates many hurdles for manufacturers in development, tech transfer and scaleup of new drugs. To illustrate how this process can have significant impact on public health, I will give example of the new drug “2-Deoxy-d-glucose” developed by DRDO which got wide publicity in the media being as brilliant breakthrough by Indian scientists in fight against COVID. The drug got approval from DCGI in the beginning of May 2021 when the wave 2 was just starting. As per the licensing procedure, after getting DCGI nod, manufacturer had to then apply for “manufacturing license” for the API and the drug product in the state where the manufacturing sites are located. Typically, the cycle time for manufacturing of API is around 1-2 months. Since without grant of license no manufacturing activity could be started, the drug product became available only by end of June 2021. In these two months India lost 1.6 lakh people to COVID. If we had the system of marketing Authorization with no restriction on manufacturing, the manufacturer could have manufactured drug in advance in anticipation of approval as is done in rest of the world and started distribution immediately after approval. If the drug was really effective in saving lives as claimed by government, it could have saved many lives.

Organization structure –

Currently FDA has apex body known as Central Drug Standards Control Organization (CDSCO) headed by Drug Controller General of India (DCGI) with 4 regional offices and 2 sub-zonal offices. Each state has State FDA bodies headed by Drug controllers / Commissioners. While CDSCO falls under Ministry of Health & family welfare of Central government. State drug control agencies fall under ministry of health of state government. There is no direct reporting of state agency to central agency, which often hampers uniform implementation of policies including the drug licensing process.

The D&C act has defined structure and responsibilities of Drugs Technical Advisory Board (DTAB), Central Drugs Laboratory (CDL) and Drugs Consultative Committee (DCC) but neither the act nor the rules clearly define the organizational structure and roles and responsibilities of Central and state organizations. Broadly Central organization is responsible for policy decisions, permission for new drug trials including clinical trials, approval of new drugs, monitoring of Adverse drug events and taking appropriate actions, grant of COPPs etc.  State FDAs are responsible for grant of manufacturing and sales and distribution licenses, periodic audits, collection of samples, enforcement actions etc. This structure makes licensing process complex especially for new drugs and for drugs meant for export which are not approved in India.

Current regulations give excessive power to DTAB in framing and modifying the rules as well as in deciding all major issues. The composition of board includes some ex-officio members, some members nominated by various government departments, educational institutions, some associations etc. This does not ensure that board members have relevant technical knowledge in various fields related to Drug development including Clinical development & trials, Manufacturing, Testing, Distribution, Quality assurance and Pharmacovigilance etc. which are crucial for taking scientifically sound decisions. Although there is provision for including additional members with specific expertise, such inclusion is left to the discretion of the board. Also, there is very little representation from the industry although the industry today has maximum knowledge in the field. While decisions related to social relevance can be taken by boards comprised of representatives of different strata through democratic process, technical decisions need to be taken with experts in specific areas.

Disregard of industry suggestions while framing new bill -

Ever since government announced its intention to amend the drug law in 2016, I have been consistently providing various inputs for improvement of drug laws directly and through associations such as IPA. I was hoping that government will consider those suggestions and in case of disagreements, initiate discussions with experts from industry before finalizing the draft. Unfortunately, after reading the draft bill 2022, it appears that none of those suggestions have been considered. The draft bill is just marginal improvement over the previous law with inclusion of section for medical devices, increase in fines etc but has shied away from making bold changes required to bring Indian law at par with global laws.

Indian pharmaceutical companies have successfully adopted and implemented drug regulations of regulatory authorities like USFDA, MHRA, TGA etc. which have been largely harmonized due to efforts by bodies like ICH, PICS and WHO. Indian drug laws including the new draft bill in contrast have not kept pace with the developments across the globe which not only deprives Indian consumers of same quality standards of medicines which are available in advanced countries but will also decimate any possibility of mutual recognition between the agencies of other countries in future. If government decides to go ahead with the draft as it is, it will be truly a missed opportunity.

Suggestions / comments on draft bill 2022.

Although all my past suggestions fell on deaf ears, as a responsible Pharmaceutical professional, I have provided following comments and suggestions to government through the e.mail address they provided. Since these suggestions are in line with my earlier suggestion, I am not sure whether they will make any impact on the committee entrusted with drafting the bill, because it is likely that the committee like DTAB, may be comprised of members lacking necessary expertise to understand the suggestions.

CHAPTER I –

Section 3: Definitions

1.      Definition of “Drug” includes substances intended for use as components of a drug including empty gelatin capsules. This will bring all the excipients used in making drug products under the definition of drug and the manufacturers of these will have to comply with requirements specified for Drugs. This is neither necessary nor practical. Even E.G capsules should not be considered as drug. It should be treated as excipient as it has no therapeutic effect.

 

CHAPTER II –

Sections 5 & 6: Drugs Technical Advisory Board and Medical devices Technical Advisory Board.

1.      The function of these boards is mentioned as “To advise Central and state governments on technical matters pertaining to Drugs and Medical devices” respectively. This statement does not provide clear guidance on what kind of matters the board is supposed to advise government on or what type of issues have to be referred to board.

2.      The composition of board includes some ex-officio members, some members nominated by various government departments, educational institutions, some associations etc. This does not ensure that board members have relevant Technical knowledge in various fields related to Drug development including Clinical development & trials, Manufacturing, Testing, distribution, Quality assurance and Pharmacovigilance etc. which are crucial for taking scientifically sound decisions on various technical matters. Although there is provision for including additional members with specific expertise, such inclusion is left to the discretion of the board. To make the process effective and scientific, this board should be eliminated, and the responsibility of any policy changes should be with CDSCO. CDSCO need to be strengthened by inducting adequate people with right technical capabilities. Committees of relevant subject matter experts may be formed from time to time to provide advice to CDSCO on specific issues.

3.      If the board has to be retained, it’s composition should include expert from all relevant fields mentioned above. Selection should be based on expertise and not because of their ex-officio positions.

Section 10: Central and State Drug laboratory, Central Medical devices testing centers

1.      The role of Central and State laboratories is not clear. All the government testing laboratories should be well equipped and of same standards so any lab can be used for performing the testing based on the proximity. This will reduce time taken in transportation of samples and minimize the adverse impact on the sample due to transportation.

Section 11: Drugs, Medical devices and Cosmetics consultative committee

1.      Instead of having such committee, the Act and Rules should be made clear so that there is no ambiguity in uniformly implementing them across the country.

Section 12:

All drugs should be treated equally to ensure that Safety and efficacy is ensured, hence such exemptions should not be allowed.

CHAPTER III: Import of the drugs

Section 14: Standard of Quality of imported drugs and cosmetics

1.      The standard of Quality should remain same for imported or locally manufactured drugs and cosmetics.

2.      Standard of Quality cannot be assured by mere testing against specification. Same should be assessed by evaluating the drug application submitted to agency in CTD format. The data submitted in the application should demonstrate that the product remain within predetermined specification, safe and effective throughout the shelf life of the product.

3.      Instead of consultation with the board for inclusion in first schedule, the law should define the approval process to be followed by CDSCO.

Section 15, 16, 17, 18, 19, 20, 21: Not of standard quality, Misbranded, Adulterated, Spurious

1.      The definitions for these terms should be common irrespective whether the drugs and cosmetics are imported or manufactured within the country. Hence instead of including them in the individual chapters, it might be better to include them in Chapter I under Sub section (3) Definitions.

2.      Determination whether the drugs are not of standard quality or adulterated cannot be done by mere physical observations and testing. There can be many unknown contaminants in the drugs and cosmetics which cannot be identified / determined by the methods specified in the definition. To ensure that the drugs are of Standard quality and are not misbranded, spurious or adulterated, they need to be manufactured in compliance to GMPs and following approved manufacturing formula and process and tested using approved testing procedures. These aspects of adherence to approved formula and procedures submitted in the application and compliance to GMPs should be part of the definitions.

Section 22: Prohibition of Import of certain drugs or cosmetics.

1.      Instead of listing out various conditions (which importer may not be in position to verify) under which the drugs or cosmetics cannot be imported, the law should simply state that No person should import any drug or cosmetic not approved by CDSCO except for personal use or for the purpose of testing and evaluation (including BE studies)

2.      Re-import of drugs exported from India, which are found to be not meeting specification upon reaching foreign country should be allowed for the purpose of destruction or re-processing.

Section 26: Power of central government to make rules under chapter III

1.      Many of these statements will become irrelevant if any drug or cosmetics to be imported in India goes through the approval process mentioned earlier.

Section 27, 28, 29: Penalty for import of drugs and cosmetics in contravention of the chapter

1.      Once import is allowed only of the drugs and cosmetics approved by CDSCO, the penalty should be for importing and distribution of unapproved drugs and cosmetics.

2.      In case of any death or injury due to use of imported material, investigation should be carried out to understand the root cause and take appropriate action. Penalty should be levied on people guilty of deliberate violation of the law or dereliction of responsibility, not otherwise.

CHAPTER IV: MANUFACTURE, SALE AND DISTRIBUTION OF THE DRUGS AND COSMETICS AND CLINICAL TRIAL OF DRUGS

Sections 33 through 40: Not of standard quality, Misbranded, Adulterated, Spurious

1.      The definitions for these terms should be common irrespective whether the drugs and cosmetics are imported or manufactured within the country.

2.      Determination whether the drugs are not of standard quality or adulterated cannot be done by mere physical observations and testing. There can be many unknown contaminants in the drugs and cosmetics which cannot be determined by the methods specified in the definition. To ensure that the drugs are of Standard quality and are not misbranded, spurious or adulterated, they need to be manufactured in compliance to GMPs and following approved manufacturing formula and process and tested using approved testing procedures. These aspects of adherence to approved formula and procedures submitted in the application and in compliance to GMPs should be part of the definitions.

Section 41: Prohibition of manufacture and sale of drugs and cosmetics

1.      Sub section (1)(a) (i) & (ii). – While manufacturing drugs or cosmetics, lots may get produced which are not of Standard Quality due various reasons like manufacturing errors, manufacturing of trial batches for establishing process etc. While sale and distribution of such lots should be prohibited, the manufacturing by itself should not be prohibited or considered as contravention. These two statements need to be modified to this effect to avoid any misinterpretation.

2.      Sub section (1)(a)(iii) – No drug whether Pharmacopoeial or Proprietary should be allowed to be distributed in India without grant of Marketing Authorization (approval) by CDSCO. All drugs proprietary or otherwise need to meet the labeling requirements as specified in labeling requirements.

3.      Sub sections (1)(a)(iv through vii) – These should be controlled through licensing (Marketing Authorization) process. Anyone distributing drugs in India without MA should be in contravention of law.

4.      Sub section(1)(c) – Sale and distribution in India before getting Marketing Authorization should be prohibited. However, manufacturing and stocking in anticipation of getting MA (License) should be allowed to facilitate launch on day 1 of Patent expiry or approval.

5.      Requirement in Sub section (1)(C) should not be applicable for drugs and cosmetics meant for exports, as sale and distribution in importing countries is controlled by respective countries laws and regulations. Countries like US, UK, EU allow manufacturing and shipping of products prior to grant of MA / ANDA approval and holding it in the country till the approval is received. This facilitates Day 1 launch in those markets which is critical for export business.

6.      Requirement in Sub section (1)(C) should not be applicable for APIs. In case of APIs even the sale should be permitted before grant of MA (license) because the APIs are not directly consumed. They need to be manufactured and supplied to drug product manufacturer for manufacturing of the finished product well before approval to meet requirement of Day 1 launch or for manufacturing development batches, exhibit batches for the purpose of testing, BE studies and clinical trials.

7.      Sub section (3) – Manufacturing of all drugs including new drugs should be permitted in anticipation of approval to facilitate Day 1 launch. Sale of drug products should be prohibited prior to getting Marketing Authorization. In case of APIs, even sale should be permitted to allow conversion into drug product for testing or in anticipation of approval.

8.      Sub section (4) – This statement appears to be out of place and should be moved to relevant chapter related to clinical trials.

9.      Sub section (5) – There should be single licensing authority either Central or state to save time and duplicity. Since drugs are distributed all over India irrespective of which state they are manufactured, for the purpose of ensuring uniform approval process, It will be advisable that all approvals are centralized.

Section 42 – Disclosure of name of manufacturer

1.      The manufacturing location for the drug product and API should be mentioned in the drug product application form (CTD format) and should be part of Marketing Authorization. Multiple manufacturing locations for full or part processing or packaging of drugs should be allowed. Requirement of printing name and address of manufacturing location should be deleted so that common packaging material inventory can be utilized irrespective of where the product is manufactured. Traceability of manufacturing location can be easily established through the Marketing authorization document, lot numbers or company records.

Section 44- Pleas relating to drugs and cosmetics

1.      Sub section 2(a) – the clause will become irrelevant if manufacturing is allowed only as per approved application which will include information about all the excipients and additives used in the drug product.

Section 45 & 46 – Government Analyst, Drug control officers

1.      These positions are relevant for import too. So instead of covering it under chapter IV, it may be prudent to include them in separate chapter.

Section 48 – Procedure for Drug control officer for sampling for testing

1.      There should requirement to ensure that the samples are stored and transported under the conditions specified on the label as improper storage and transportation conditions can have significant impact on the test results.

2.      Drug control officer should also record the conditions at which the drug was stored at the premises from where the sample was collected.

Section 52 – Report of Government analyst

1.      There should be requirement for time limit for completion of analysis and storage of the samples as per labeled storage condition till analysis is completed.

2.      There should be requirement for secure data storage including electronic data and investigation of Out of specification results.

3.      There should be provision for joint analysis if results of government analysts and manufacturer are significantly different, because execution of test methods many times require specific skills and qualification.

Section 54 – Powers of Central Government to prohibit manufacture etc. of Drugs and cosmetics

1.      This should be ensured at the time of approval of drug application. If post approval PV data indicate safety or efficacy concerns, the approval should be withdrawn.

Section 56 & 57 –

1.      It is possible that in spite of best efforts, drugs and cosmetics falling under definition of Adulterated or Not of standard Quality may get accidentally distributed in the market or during the shelf life deteriorate to fall under these definitions. If such incidence comes to the notice of the MA holder, they should be encouraged to report same to the Drug control agency and initiate recall to safeguard patients. Imposing heavy penalties & prison terms may drive MA holders to hide information resulting in not recalling such product from market which in turn may have adverse impact on the patients.

2.      Penalties should be imposed for deliberately distributing such drugs and not reporting / recalling in timely manner.

Sections 72 through 81– Clinical trials

1.      It will be prudent to include these requirements in separate chapter instead of Chapter IV.

First Schedule

1.      This schedule should be scrapped. The standards to be followed should be as given in the approved drug application. The standards proposed by the manufacturer should be scientifically justified and should be approved by CDSCO as part of drug approval process.

2.      Labeling requirements for different types of the drugs should be defined in section for labeling.

Fourth schedule

1.      This schedule is not relevant. The testing should be done as per the approved monograph hence not really required to define categories for NSQ and misbranded in the schedule.

 

 

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